Antigen Levels Research Articles

Structure-Activity Relationships and Discovery of (S)-5-(tert-Butyl)-11-(difluoromethoxy)-9-methoxy-2-oxo-1,2,5,6-tetrahydropyrido[2',1':2,3]imidazo[4,5-h]quinoline-3-carboxylic Acid (AB-161), a Novel Orally Available and Liver-Centric HBV RNA Destabilizer.

Lowering hepatitis B surface antigen (HBsAg) levels from covalently closed circular DNA (cccDNA) and the integrated genome could reduce the persistence of hepatitis B virus (HBV) infection. Since HBV replication occurs in the liver and to ameliorate the peripheral neuropathy observed with a first-generation tricyclic 4-pyridone PAPD5/7 inhibitor (AB-452) having high systemic exposure, we focused on increasing the hepatocyte concentration and reducing plasma levels. Optimization of a novel series of PAPD5/7 inhibitors that decrease HBsAg levels led to the tetracyclic 2-pyridone AB-161, which was similarly potent to AB-452 in vitro and in vivo but showed dramatically higher rodent liver-to-plasma ratios. There were no neurobehavioral effects with AB-161 in dogs up to 45 mg/kg after 60 days, unlike with AB-452, where these were observed at lower doses by day 14. AB-161 was then advanced into 90-day GLP toxicology studies, where the improved neurotoxicity profile persisted, but reproductive issues emerged, leading to discontinuation.

Case report: A golden tail of immunotherapy: significant tail effect in a chemotherapy-resistant advanced pulmonary sarcomatoid carcinoma patient treated by Sintilimab combined with Anlotinib

Tail effect is a unique phenomenon in immunotherapy characterized by the prolonged maintenance of therapeutic efficacy. It can be observable even after treatment cessation. Immunotherapy has gradually become a vital regimen for the treatment of advanced lung cancer patients, among which immune-combined therapies based on immune checkpoint inhibitors (ICIs) have been applied clinically and demonstrates considerable clinical efficacy. In this case report, the patient was pathologically diagnosed with pulmonary sarcomatoid carcinoma (PSC), a rare and highly aggressive subtype of non-small cell lung cancer (NSCLC) known for its poor prognosis due to high invasiveness and metastatic potential. After developing resistance to chemotherapy, the patient was treated with a combined regimen of sintilimab and anlotinib, leading to initial clinical improvement. Following just three cycles of this regimen, treatment was discontinued, and the patient was discharged. Remarkably, over the subsequent months, the patient exhibited a significant tail effect, evidenced by sustained therapeutic stability, continuous tumor regression, stable low levels of serum carcinoembryonic antigen (CEA), and further improvement in clinical symptoms. Tail effect is a golden tail of immunotherapy. This case illustrates that the tail effect of immunotherapy can offer substantial survival benefits for patients with unresectable advanced lung cancer who have failed chemotherapy.

Laboratory and Molecular Diagnosis of Factor XI Deficiency.

The prevalence of factor XI (FXI) deficiency is 1 per 10 to 20,000 in the general population, much higher than that reported in most texts. The prevalence is higher in Ashkenazi Jews where it is about 1:20. Clinically, FXI deficiency presents as a mild bleeding disorder mostly associated with posttraumatic or postsurgical hemorrhages or unexplained minor bleeding. It is often discovered due to incidental finding of a prolonged activated partial thromboplastin time (aPTT) on routine laboratory screening. FXI deficiency is an autosomal recessive bleeding disorder with many causative F11 gene defects. Diagnosis is based on FXI activity, antigen levels, and molecular diagnostics. As FXI levels do not correlate with bleeding symptoms, identification of pathogenic genetic variants may be a more accurate predictor of bleeding risk and therefore aid in the clinical management of the patient. Two variants in the F11 gene account for most cases found in the Jewish and Arab populations. Patients with FXI deficiency can develop inhibitors to FXI although spontaneously acquired inhibitors are extremely rare. We will discuss laboratory and molecular assays used to diagnose FXI deficiency as well as interferences that can complicate diagnosis including new anticoagulants and acquired FXI inhibitors.

Adenocarcinoma of unknown primary presenting with congestive heart failure in a middle-aged Ethiopian woman: a case report

BackgroundHeart failure is a rare manifestation of metastatic disease of the carcinoma of an unknown primary, malignancy that requires extensive work-up to identify the primary site. Initial consideration of rare etiologies in patients presented with a common clinical syndrome is challenging.Case presentationA 35-year-old Black woman presented with shortness of breath at rest, orthopnea, paroxysmal nocturnal dyspnea, chest pain, a blood-tinged productive cough, and fever for 2 weeks. She also had progressive body swelling, easy fatigability, loss of appetite, and abdominal pain during the same week’s duration. Body imaging revealed large pleural and pericardial effusions, metastatic liver lesions, and bilateral pulmonary vascular segmental and subsegmental filling defects. Pericardial and pleural fluid cytology suggest malignant effusion. Liver lesions and core needle biopsy indicated adenocarcinoma of unknown origin, and the carcinoembryonic antigen level also increased significantly.ConclusionCarcinoma of unknown primary origin commonly presents in an advanced stage and is often accompanied by clinical features of site metastasis. This case highlights heart failure as an unusual first manifestation of adenocarcinoma with an unknown primary origin.

Interdependence of coagulation with immunotherapy and BRAF/MEK inhibitor therapy: results from a prospective study

Immune checkpoint inhibitor (ICI) therapies effectively treat a broadening spectrum of cancer entities but induce various immune-related side effects (irAEs). Recent reports suggest a correlation between ICI-induced systemic inflammation and thromboembolic events as well as an increased effectiveness by coadministration of anticoagulants. With cancer patients having a higher risk of thrombotic events per se, it is crucial to dissect and characterize the mechanisms that cause pro-coagulative effects induced by systemic tumor therapies and their potential interplay with anti-tumor response. A total of 31 patients with advanced skin cancer treated with either ICIs (n = 24) or BRAF/MEK inhibitors (n = 7) were longitudinally assessed for blood and coagulation parameters before as well as 7, 20 and 40 days after initiation of systemic tumor therapy. Changes were analyzed and compared between both groups. In addition, the influence of coagulation parameters on progression-free, recurrence-free and overall survival was investigated. The ICI cohort presented significantly increased factor VIII activity after one week of therapy (p 0.0225); while, protein S activity was reduced during the whole observation period. Additionally, von Willebrand factor activity and tissue factor concentrations increased under immunotherapy. Similar changes occurred under BRAF/MEK inhibitor therapy (BRAF/MEKi). Increased baseline levels of von Willebrand factor antigen and factor VIII:C before the start of ICI therapy correlated with a significantly higher risk of recurrence for patients receiving adjuvant immunotherapy. The findings suggest the induction of a pro-coagulant state under ICI and BRAF/MEKi and a role of coagulation parameters in the efficacy of ICI therapies.

Prostate-specific antigen, digital rectal examination, and prostate cancer detection: A study based on more than 7000 transrectal ultrasound-guided prostate biopsies in Ghana

Purpose of the studyThis study aims to determine the role of serum prostate-specific antigen (PSA) levels and digital rectal examination (DRE) in predicting the histological outcomes of prostate biopsies by analyzing a database of over 7000 patients who underwent transrectal ultrasound (TRUS)-guided prostate biopsies. MethodsWe conducted a retrospective analysis of men who underwent TRUS-guided prostate biopsies at Korle Bu Teaching Hospital, a tertiary referral center in Accra, Ghana, from July 2005 to December 2022. The biopsies, which included 10 to 12 core samples, were prompted by PSA levels greater than 4.0 ng/mL, abnormal DRE findings, or both. We then correlated histopathology results with PSA and DRE findings. ResultsOut of 7,338 patients who presented for biopsy, 76.3% were between the ages of 60 and 79. Histology reports were available for 5,289 patients, of whom 2,564 (48.5%) were diagnosed with prostate cancer. Cancer detection rates based on PSA levels were as follows: 21.6% for PSA <4 ng/mL, 21.7% for PSA 4-10 ng/mL, 32.7% for PSA 10-20 ng/mL, 53.0% for PSA 20-50 ng/mL, 71.5% for PSA 50-100 ng/mL, and 92.0% for PSA >100 ng/mL. When DRE findings were classified according to the 2016 TNM System (AJCC 8th Edition) as T1, T2, T3, and T4, cancer detection rates were 26.8%, 51.8%, 87.6%, and 95.7%, respectively. The overall cancer detection rate was significantly higher with abnormal DRE findings (64.6% vs. 26.7%, p < 0.001). Additionally, 78.2% of the detected cancers were high-grade (Gleason score of 7 or more). ConclusionThis extensive study of Ghanaian men undergoing TRUS biopsies reveals a high prostate cancer detection rate, with nearly 80% of the detected cancers being high-grade. These findings underscore the importance of PSA and DRE in the early detection of prostate cancer and should be considered in patient counseling and discussions regarding the implementation of prostate cancer screening programs in this population.

Androgen Receptor Signaling Inhibitor Withdrawal Syndrome After Castration-resistant Prostate Cancer.

Androgen-deprivation therapy is an extremely effective treatment for progressive prostate cancer. Previously, the first-line treatment for progressive prostate cancer was combined androgen blockade (CAB). If the disease progressed to castration-resistant prostate cancer, the administration of androgen receptor signaling inhibitors (ARSIs) was recommended. When elevated serum prostate-specific antigen (PSA) levels are seen during CAB treatment, it is important to suspect antiandrogen withdrawal syndrome (AWS), discontinue CAB, and monitor the changes in the serum PSA levels. If a reduction in the patient's PSA levels is subsequently observed, antiandrogens should be discontinued and the patient should be followed, but if their PSA level rises they should be transitioned to ARSI treatment. Recently, there have been reports of withdrawal syndrome (WS) after ARSI treatment. With the increased use of ARSIs, such as abiraterone acetate, enzalutamide, apalutamide, and dalorutamide, it is necessary to consider ARSI WS when a patient's serum PSA level increases during ARSI treatment. Unnecessary treatment can be avoided if the confirmation of ARSI WS is prioritized. Conversely, if it is not confirmed there is a risk that second-line treatment will be delayed. This is a review of recent studies of ARSI WS. It also discusses future prospects in this field.

The severe von Willebrand Disease variant p.M771V leads to impaired anterograde trafficking of Von Willebrand factor in patient-derived and base-edited ECFCs

BackgroundVon Willebrand disease (VWD) is the most common inherited bleeding disorder caused by quantitative or qualitative defects of VWF. The p.M771V VWF variant leads to a severe bleeding phenotype in homozygous patients. However, the exact molecular mechanism remains unclear, which prevents personalized treatment of those VWD patients. ObjectiveThis study aims to characterize the underlying molecular mechanisms of the p.M771V variant in multiple representative ex-vivo cell models. MethodsECFCs were isolated from venous blood of VWD patients from the Willebrand in the Netherlands (WiN) cohort carrying homozygous and heterozygous p.M771V VWF variants. The p.M771V variant was also introduced in cord-blood derived ECFCs (CB-ECFCs) through adenine base editing and was overexpressed in HEK293 cells. Biosynthesis, storage, and secretion of VWF was studied using biochemical methods and confocal microscopy. ResultsTwo unrelated homozygous p.M771V patients presented with very low VWF activity and antigen levels in plasma. Patient ECFCs showed impaired proVWF processing into mature VWF with secreted VWF being severely reduced when compared to ECFCs of healthy donors. Multimer analysis of p.M771V ECFCs showed a deficiency of high molecular weight VWF multimers. Immunofluorescent staining revealed VWF retention in the endoplasmic reticulum (ER); this was confirmed in various populations of base edited CB-ECFCs harboring the p.M771V variant. ConclusionThe severe endothelial phenotype observed in patient-derived p.M771V ECFCs, HEK293 cells, and an original base-edited CB-ECFC modelling system, show that ER retention of VWF and failure to undergo subsequent proteolytic processing underpins the severe bleeding phenotype of patients with homozygous variants at M771.

Proton pump inhibitor attenutes acidic microenvironment to improve the therapeutic effects of MSLN-CAR-T cells on the brain metastasis of solid tumors

The incidence of brain metastasis (BM) is gradually increasing, and the prognosis and therapeutic effect are poor. The emergence of immunotherapy has brought hope for the development of BM treatments. This study revealed that compared with primary cancers (PCs), BMs have a “colder” and more acidic tumor microenvironment (TME), resulting in reduced protein levels of mesothelin (MSLN), a promising target for chimeric antigen receptor-T (CAR-T) cell therapy for triple-negative breast cancer (TNBC) with BMs. These factors could significantly decrease the efficiency of MSLN-CAR-T cells in TNBC BMs. Pantoprazole (PPZ) administration at the most commonly used dose in the clinic notably increased the pondus hydrogenii (pH) of the TME, inhibited lysosomal activity, increased the membrane levels of the MSLN protein and improved the killing ability of MSLN-CAR-T cells both in vitro and in vivo. Similar results were obtained in non-small cell lung cancer (NSCLC) BMs. Hence, when administered in combination with CAR-T cells, PPZ, which increases the protein levels of target antigens, may constitute a new immunotherapeutic strategy for treating solid tumors with BMs.

Nomogram Analysis for Predicting Response to Androgen‐Receptor‐Axis‐Targeted Therapies in Patients With Metastatic Castration‐Resistant Prostate Cancer

ABSTRACTBackgroundThis study aimed to identify the clinical predictors for the response of patients with mCRPC to ARATs.Materials and MethodsWe retrospectively collected data on consecutive patients who were diagnosed with mCRPC and underwent ARAT treatment during this stage of the disease. Clinical parameters were obtained through medical chart reviews. ARAT failure was defined as a continuous increase in the serum prostate‐specific antigen (PSA) level above nadir to &gt; 2 ng/mL, accompanied by radiographic progression. ARAT failure‐free survival and overall survival were assessed through Kaplan–Meier survival analysis and Cox regression survival analysis. Nomogram analysis based on significant predictors of ARAT failure‐free survival was performed.ResultsIn total, 319 patients with mCRPC who underwent ARAT were included. Multivariate analysis revealed that age, International Society of Urological Pathology (ISUP) grading, and chemotherapy‐naïve status were significant predictors of ARAT failure‐free survival. For overall survival, age, ISUP grading, and nadir PSA level during androgen deprivation therapy (ADT) were significant predictors. Through nomogram analysis based on age, ISUP grading, and chemotherapy‐naïve status, the likelihood of ARAT duration being more or less than 1 year could be predicted.ConclusionFor mCRPC patients, being older, having ISUP Grade 5 cancer, and having a history of chemotherapy were associated with a shorter duration of response to next‐line ARATs. Therefore, other therapeutic agents should be prioritized for such patients. Notably, among the included patients, those who were older, had a higher ISUP grade and a higher nadir PSA level during ADT exhibited worse overall survival.

Detecting Clinically Significant Prostate Cancer in PI-RADS 3 Lesions Using T2w-Derived Radiomics Feature Maps in 3T Prostate MRI

Prostate Imaging Reporting and Data System version 2.1 (PI-RADS) category 3 lesions are a challenge in the clinical workflow. A better detection of the infrequently occurring clinically significant prostate cancer (csPCa) in PI-RADS 3 lesions is an important objective. The purpose of this study was to evaluate if feature maps calculated from T2-weighted (T2w) 3 Tesla (3T) MRI can help detect csPCa in PI-RADS category 3 lesions. In-house biparametric 3T prostate MRI examinations acquired between January 2019 and June 2023 because of elevated prostate-specific antigen (PSA) levels were retrospectively screened. Inclusion criteria were a PI-RADS 3 lesion and available results of an ultrasound-guided targeted and systematic biopsy. Exclusion criteria were a simultaneous PI-RADS category 4 or 5 lesion and hip replacement. Target lesions with the International Society of Urological Pathology (ISUP) grade group 1 were rated clinically insignificant PCa (ciPCa) and ≥2 csPCa. This resulted in 52 patients being included in the final analysis, of whom 11 (21.1%), 8 (15.4%), and 33 (63.5%) patients had csPCa, ciPCa, and no PCa, respectively, with the latter two groups being combined as non-csPCa. Eight of the csPCas were located in the peripheral zone (PZ) and three in the transition zone (TZ). In the non-csPCa group, 29 were located in the PZ and 12 in the TZ. Target lesions were marked with volumes of interest (VOIs) on axial T2w images. Axial T2w images were then converted to 93 feature maps. VOIs were copied into the maps, and feature quantity was retrieved directly. Features were tested for significant differences with the Mann–Whitney U-test. Univariate models for single feature performance and bivariate models implementing PSA density (PSAD) were calculated. Ten map-derived features differed significantly between the csPCa and non-csPCa groups (AUCs: 0.70–0.84). The diagnostic performance for TZ lesions (AUC: 0.83–1.00) was superior to PZ lesions (AUC: 0.74–0.85). In the bivariate models, performance in the PZ improved with AUCs &gt;0.90 throughout. Parametric feature maps alone and as bivariate models with PSAD can (?) noninvasively identify csPCa in PI-RADS 3 lesions and could serve as a quantitative tool reducing ambiguity in PI-RADS 3 lesions.

Investigating High-risk Factors, Precise Diagnosis, and Treatment of Castration- Resistant Prostate Cancer (CRPC).

The treatment of metastatic castration-resistant prostate cancer (mCRPC) in the actual world currently presents difficulties. In light of this, it is crucial to investigate high-risk factors for the progression of advanced prostate cancer and to identify methods for delaying the onset of CRPC. This study aimed to explore the high-risk factors that impact the progression of prostate cancer and emphasize the significance of precise diagnosis and treatment based on etiological classification in the clinical management of castration-resistant prostate cancer. A retrospective analysis was conducted on 277 newly diagnosed cases of PCa treated with endocrine therapy. A follow-up was done on prostate-specific antigen (PSA) levels and testosterone. Additionally, a prospective analysis was performed on the clinical data of 60 patients with CRPC. Following the principle of "4W1H", 30 patients were included in the precision treatment group for a second biopsy and related tests, while another 30 patients were included in the conventional treatment group. The therapeutic effect and prognosis of the two groups were observed. Distant metastasis (HR = 1.879, 95% CI: 1.311 ~ 2.694, P = 0.001), PSA nadir > 0.2 ng/mL (HR = 1.843, 95% CI: 1.338 ~ 2.540, P = 0.001), testosterone nadir > 20 ng/dL (HR = 1.403, 95% CI: 1.035 ~ 1.904, P = 0.029), and time to testosterone nadir > 6 months (HR = 1.919, 95% CI: 1.364 ~ 2.701, P = 0.001) were risk factors for the progression to CRPC. Patients in the CRPC group were treated with precision therapy and conventional therapy based on their molecular subtyping. The precision treatment group showed a significantly prolonged median PSA progression-free survival compared to the conventional treatment group (16.0 months vs. 13.0 months, P=0.025). The median radiographic progression-free survival was also significantly extended in the precision treatment group compared to the conventional treatment group (21.0 months vs. 16.0 months, P=0.042). Patients with prostate cancer diagnosed with distant metastasis at initial presentation require early intervention. Close monitoring of PSA and serum testosterone changes is necessary during the process of endocrine therapy. After entering the CRPC stage, the etiological classification precision treatment can improve the therapeutic effect and improve the prognosis of patients.

Survival Benefits of Postoperative Chemotherapy in Patients With Colorectal Mucinous Adenocarcinoma: An Analysis Utilizing Propensity Score Matching From the Surveillance, Epidemiology, and End Results Database.

This study aimed to investigate the characteristics of patients with colorectal mucinous adenocarcinoma (MAC) who benefit from postoperative chemotherapy (POCT) and to develop effective postoperative survival nomograms for predicting overall survival (OS) in colorectal MAC patients. Data of colorectal MAC patients who underwent surgery from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2020 were collected. Patients were grouped based on POCT, and intergroup analysis was performed using 1:1 propensity score matching (PSM). Kaplan-Meier (K-M) curves were used to compare the prognosis between the 2 groups. Cox analysis was employed to identify factors associated with OS in patients with colorectal MAC who underwent POCT. The variance inflation factor (VIF) and bilateral stepwise regression were used to determine factors included in the model. Additionally, a nomogram was constructed to predict postoperative survival outcomes for patients. The discriminative ability of the nomograms was evaluated using the C-index and calibration curve analysis, the decision curve analysis (DCA) assessed the clinical utility of the nomogram, and the receiver operating characteristic (ROC) curve evaluated the nomograms' performance. This study encompassed 6829 patients with colorectal MAC, among whom 2258 received POCT, and 4571 did not. Whether pre or post PSM, patients in the POCT group consistently exhibited a superior median OS compared to those in the postoperative non-chemotherapy group (P < .0001). For colorectal MAC patients undergoing POCT, OS was correlated with factors such as patient age, carcinoembryonic antigen levels, tumor deposits, perineural invasion (PNI), lymph node examination count, T staging, and Grade staging. Notably, a significant chemotherapy advantage was observed in patients without perineural invasion, those with lymph node examination counts exceeding 12, and patients with moderately differentiated tumors. The overall colorectal MAC patient postoperative OS predictive nomogram demonstrated a C-index of .74, with a calibration curve near the diagonal and a DCA curve indicating positive net benefits. In comparison to TNM staging, the ROC curves of the nomogram at 1 year, 3 years, and 5 years demonstrated superior predictive capabilities (AUC: .80 vs .71, .78 vs .71, .77 vs .70). This study revealed the characteristics of colorectal MAC patients who benefit from POCT and established effective prognostic nomograms, which can aid clinicians in designing personalized treatment plans for individual patients and promote precision medicine.

Monitoring of Viral Infections in Vegetable Crops in Agroecosystems of Ukraine

Information on the abundance and diversity of phytopathogenic viruses in Ukraine is very variable and limited. There is a high importance of a complex study of the species composition and ways of spreading crop viruses, as well as the development of epiphytotic forecasting systems, which will help to limit the ranges of these viruses and save crop yields. Consequently, the aim of our study was to explore the species composition and frequency of mono- and mixed virus infection of vegetable crops in Ukrainian agrocenoses and to identify the possible etiology of its occurrence. Methods. The samples were analyzed for the presence of viral antigens by enzyme-linked immunosorbent assay in sandwich and indirect modifications. For the detection of viral antigens in ELISA, test systems manufactured by Loewe were used. To identify the virus, the material was homogenized and purified, and then registered on a reader. Results. The frequency of vegetable crops damaged by diseases of viral etiology increased by 25–27% compared to the previous years of the study. Serological analysis showed that 59% of the studied samples of the Cucurbitaceae family and 54% of the Solanaceae family were affected by the main viral diseases most common in Ukraine. The seed way of transmission of vegetable viruses in Ukraine was demonstrated as one of the sources of viruses in agrocenoses. The presence of antigens to cucumber mosaic virus (CMV) in 14.3% of the studied seeds, zucchini yellow mosaic virus (ZYMV) – 11.2%, and tomato mosaic virus (ToMV) – 12.6% was shown. This allows us to suggest that sowing those seeds in the future will contribute to the spread of these viruses across Ukraine. Analysis of soil samples showed the presence of antigens of cucumber mosaic virus, tobacco mosaic virus, and potato virus X. The lowest level of antigens to CMV was detected in the soils of Vinnytsia region, to PVX – in the Kyiv and Cherkasy regions, and to TMV – in the Odesa region. Conclusions. Vegetable agrocenoses in Ukraine are more often affected by viruses belonging to the Tobamovirus, Cucumovirus, Potyvirus, and Tospovirus genera of the Bromoviridae, Potyviridae, and Bunyaviridae families. In addition to the increasing areas of viral monoinfection, there is an active spread of mixed infection, or "superinfection", in Ukrainian agrocenosis. Mixed infections are mainly formed during the growth and development of the tested vegetable crops. All of this leads to further significant spread of not only mono- but also mixed virus infection of vegetable crops.

Advancing prostate cancer detection: High-accuracy urine test distinguishes between high and low-risk cancers

Prostate cancer remains one of the leading causes of cancer-related deaths among men. The standard method for early detection involves measuring Prostate-specific antigen (PSA) levels in the blood, with elevated PSA levels prompting further diagnostic procedures, such as a prostate biopsy. While effective, biopsies can be painful and carry risks of complications such as fever and urinary tract infections. To reduce unnecessary biopsies, researchers have sought alternative diagnostic methods. In recent years, a urine test was developed for early-stage prostate cancer detection. However, this test struggled to differentiate between aggressive and slow-growing cancers, the latter of which often require minimal treatment and are managed through active surveillance. To address this limitation, scientists at Wunderkind University have significantly enhanced the urine test. By analysing the genomes of thousands of prostate cancer patients, they identified a panel of 16 genes detectable in urine that can effectively distinguish between high-risk and low-risk cancers. When applied to individuals with elevated PSA levels, this improved test demonstrated an impressive 97% accuracy in identifying advanced prostate cancer. This advancement holds great promise for reducing unnecessary biopsies and improving patient outcomes by accurately identifying those needing aggressive treatment versus those suitable for observation. This review paper will explore the development, validation, and clinical implications of this novel urine test, highlighting its potential to transform prostate cancer diagnostics and patient management.

G-Protein-Coupled Receptor-Associated Sorting Protein 1 Overexpression Is Involved in the Progression of Benign Prostatic Hyperplasia, Early-Stage Prostatic Malignant Diseases, and Prostate Cancer

Background/Objectives: Prostate cancer (PCa) is a prevalent malignancy, necessitating accurate diagnostic methods to distinguish it from benign conditions such as benign prostatic hyperplasia (BPH). Current diagnostic tools, relying primarily on serum prostate-specific antigen (PSA) levels, lack specificity, leading to an over-diagnosis and unnecessary treatment of patients with benign conditions. This study explores G-protein-coupled receptor-associated sorting protein 1 (GASP-1) as a more sensitive biomarker for PCa detection. Methods: Prostate tissue microarrays of healthy, BPH, and prostate cancer patients with different Gleason scores were studied. Polyclonal antibodies targeted against GASP-1 were used for routine immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) analyses. Results: The results indicated a 5-fold difference in serum GASP-1 levels between BPH and PCa, which was validated through GASP-1 IHC. Furthermore, a novel scoring system, the H-score, assesses GASP-1 granules’ intensity and size, revealing a clear distinction between BPH and PCa. An additional analysis of GASP-1 expression between PCa cases with different Gleason scores reveals that GASP-1 overexpression correlates with PCa severity, providing insights into disease progression. Conclusions: The study supports GASP-1′s role as a promising diagnostic marker, supplementing PSA testing, and offering improved risk stratification for PCa. Additionally, an open-source software system is introduced for an efficient GASP-1 granule color analysis, enhancing diagnostic accuracy.

Oncological Outcomes of Partial Gland Ablation Using High-Intensity Focused Ultrasound After Additional Confirmatory Transperineal Mapping Biopsy in Men with Prostate Cancer

Background/Objectives: To evaluate whether additional confirmatory transperineal mapping biopsy (TPMB) in men with localized prostate cancer (PCa) alters the treatment plan and outcome of partial gland ablation (PGA) using high-intensity focused ultrasound (HIFU). Methods: We retrospectively reviewed data from 96 patients who underwent PGA using HIFU between January 2020 and June 2022. After multiparametric magnetic resonance imaging (mpMRI), all men underwent transrectal ultrasound (TRUS)-guided, cognitive-targeted biopsy and systematic biopsy. Men eligible for PGA using HIFU first underwent confirmatory TPMB. Any changes in the treatment plan after TPMB were analyzed. Follow-up TRUS-guided biopsy was performed 1 year post-operatively to evaluate oncological outcomes. Clinically significant PCa (csPCa) was defined as Gleason grade (GG) ≥ 2. Results: Among all subjects, the median age (IQR) was 65.0 (60.0–72.0) years and the prostate-specific antigen level was 5.20 (3.71–7.81) ng/mL. The results of both TRUS-guided biopsy and TPMB led to a change in the treatment plan (from unilateral to bilateral PGA) for 13 (13.5%) patients. The 1-year follow-up TRUS-guided biopsy identified PCa in 13 (13.5%) patients, and csPCa in 7 (7.3%) patients. The infield- and outfield-positive rates were 8.3% (8/96) and 3.1% (3/96), respectively, for any PCa, and 3.1% (3/96) and 2.1% (2/96), respectively, for csPCa. Conclusions: Confirmatory TPMB results in better disease identification and localization, thereby affecting the treatment plan and improving oncological outcomes. Therefore, confirmatory TPMB should be considered to establish an appropriate strategy for patients with localized PCa eligible for PGA using HIFU.

Primary seminal vesicle diffuse large B-cell lymphoma: a case report and review of the literatures

Primary seminal vesicle lymphoma is a remarkably rare condition, predominantly manifesting as diffuse large B-cell lymphoma. Due to its rarity and nonspecific clinical presentations, it is often misdiagnosed or overlooked. Here, we report a case of a 68-year-old male diagnosed with primary seminal vesicle lymphoma, coinciding with prostate cancer. The diagnosis followed initial findings of elevated prostate-specific antigen levels and abnormal magnetic resonance imaging of the prostate and left seminal vesicle. Suspicion of prostate cancer led to a radical resection of both the prostate and seminal vesicle. Subsequent pathological examination and next-generation sequencing post-surgery confirmed the diagnosis of primary seminal vesicle diffuse large B-cell lymphoma, characterized by CD79B mutation type (MCD type). The patient was treated with six cycles of the R-CHOP regimen (rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone), achieving complete metabolic remission as confirmed by positron emission tomography-computed tomography. Fifteen months post-treatment, the patient’s condition remains favorable. Through our literature review of additional six cases of primary seminal vesicle lymphoma, we aim to elucidate the typical clinical presentations, imaging features, pathological characteristics, genetic mutations, and therapeutic strategies, aiming to contribute to better detection and management of this rare malignancy. This case underscores the diagnostic challenges and emphasizes the necessity for heightened clinical suspicion and definitive pathological examination in the management of primary seminal vesicle lymphoma.

Dysphasia: metastatic prostate cancer to the leptomeninges: a case report

BackgroundLeptomeningeal metastasis occurs in 5% of patients with prostate cancer and indicates a very poor prognosis.Case presentationA 60-year-old Caucasian male patient diagnosed with metastatic castration-resistant prostate cancer with sclerotic bone metastases and soft tissue metastases underwent multiple courses of chemotherapy and hormone therapy. The diagnosis of prostate cancer is based on elevated prostate-specific antigen levels and tissue biopsy. He subsequently presented with expressive aphasia. Nonspecific, diffuse irregular dural/pachymeningeal thickening enhancement was noted on magnetic resonance imaging. Upon evaluation by neurology, electroencephalogram was negative for an epileptiform correlate. The workup included a lumbar puncture to rule out infectious etiology. The patient’s neurological status stabilized, and he was discharged home with a plan for continued therapy with abiraterone and prednisone. Due to advanced malignancy, the patient enrolled in hospice and died 3 weeks after hospital discharge.ConclusionsCentral nervous system metastasis occurs very rarely in prostate cancer. With the increase in life expectancy and advances in oncologic therapy for prostate cancer, physicians should be aware of and consider central nervous system metastasis in men aged 50 years and above.

Factor X consumption attenuates the coagulation effect of emicizumab: a case of severe hemophilia A treated with emicizumab and factor VIII-bypassing agents.

In patients with hemophilia A with inhibitor (PwHA-I), emicizumab drastically reduces bleeding events. However, few studies have investigated the behavior and effects of factor X (FX) in patients who require intensive treatment with factor VIII-bypassing agents (BPA) and emicizumab. A 59-year-old man with HA-I receiving emicizumab prophylaxis was admitted to our hospital because of acute gangrenous cholecystitis. He received percutaneous transhepatic gallbladder drainage and laparoscopic cholecystectomy along with repeated administration of recombinant activated factor VII (rFVIIa). On day 10, a large hematoma developed around the residual gallbladder. Rotational thromboelastometry (ROTEM) suggested poor effect of rFVIIa and reduced activity of emicizumab. Considering that this could be due to consumption of FX, plasma-derived FVIIa/FX agent (pdFVIIa/X) was administered, and ROTEM parameters recovered considerably. The patient was discharged on day 19 uneventfully. Plasma assays revealed that FX antigen level (FX:Ag) was 107.5% at baseline but then decreased. Administration of pdFVIIa/FX restored FX:Ag (pre/post 47.2%/125.5%). ROTEM and thrombin generation assay with in vitro addition of anti-emicizumab antibody suggested that low FX:Ag was responsible for attenuating the effect of emicizumab, and pdFVIIa/FX administration restored coagulation potentials. In PwHA-I receiving intensive treatment with rFVIIa under emicizumab prophylaxis, FX consumption might attenuate the effect of emicizumab.